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889 results on '"Leleu, X."'

2. French early nationwide idecabtagene vicleucel chimeric antigen receptor T‐cell therapy experience in patients with relapsed/refractory multiple myeloma (FENIX): A real‐world IFM study from the DESCAR‐T registry.

Author

Ferment, B., Lambert, J., Caillot, D., Lafon, I., Karlin, L., Lazareth, A., Touzeau, C., Leleu, X., Moya, N., Harel, S., Perrot, A., Bories, P., Vincent, L., Lamure, S., Mohty, M., Malard, F., Manier, S., Yakoub‐Agha, I., Schiano De Colella, J.‐M., and Brisou, G.

Subjects
CYTOKINE release syndrome, BISPECIFIC antibodies, CHIMERIC antigen receptors, PATIENT experience, MULTIPLE myeloma
Abstract

Summary: Idecabtagene vicleucel (ide‐cel), a chimeric antigen receptor T‐cell therapy targeting B‐cell maturation antigen (BCMA), received early access program (EAP) authorization in France in April 2021 for relapsed/refractory multiple myeloma (RRMM). We conducted a real‐world registry‐based multicentre observational study in 11 French hospitals to evaluate ide‐cel outcomes. Data from 176 RRMM patients who underwent apheresis between June 2021 and November 2022 were collected from the French national DESCAR‐T registry. Of these, 159 patients (90%) received ide‐cel. Cytokine release syndrome occurred in 90% with 2% grade ≥3, and neurotoxicity occurred in 12% with 3% grade ≥3. Over the first 6 months, the best overall response and ≥complete response rates were 88% and 47% respectively. The median progression‐free survival (PFS) from the ide‐cel infusion was 12.5 months, the median overall survival (OS) was 20.8 months and the estimated OS rate at 12 months was 73.3%. Patients with extra‐medullary disease (EMD) had impaired PFS (6.2 months vs. 14.8 months). On multivariable analysis, EMD and previous exposure to BCMA‐targeted immunoconjugate or T‐cell‐redirecting GPRC5D bispecific antibody were associated with inferior PFS. Our study supports ide‐cel's feasibility, safety and efficacy in real‐life settings, emphasizing the importance of screening for EMD and considering prior treatments to optimize patient selection. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone in patients with relapsed and refractory multiple myeloma: final overall survival analysis

Author

Richardson, PG, Perrot, A, Miguel, JS, Beksac, M, Spicka, I, Leleu, X, Schjesvold, F, Moreau, P, Dimopoulos, MA, Huang, S-Y, Minarik, J, Cavo, M, Prince, HM, Macé, S, Zhang, R, Dubin, F, Morisse, MC, Anderson, KC, Richardson, PG, Perrot, A, Miguel, JS, Beksac, M, Spicka, I, Leleu, X, Schjesvold, F, Moreau, P, Dimopoulos, MA, Huang, S-Y, Minarik, J, Cavo, M, Prince, HM, Macé, S, Zhang, R, Dubin, F, Morisse, MC, and Anderson, KC

Abstract

The primary and prespecified updated analyses of ICARIA-MM (clinicaltrial gov. Identifier: NCT02990338) demonstrated improved progression-free survival (PFS) and a benefit in overall survival (OS) was reported with the addition of isatuximab, an anti-CD38 monoclonal antibody, to pomalidomide-dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma. Here, we report the final OS analysis. This multicenter, randomized, open-label, phase III study included patients who had received and failed ≥2 previous therapies, including lenalidomide and a proteasome inhibitor. Between January 10, 2017, and February 2, 2018, 307 patients were randomized (1:1) to isatuximab-pomalidomide-dexamethasone (Isa-Pd; N=154) or Pd (N=153), stratified based on age (<75 vs. ≥75 years) and number of previous lines of therapy (2-3 vs. >3). At data cutoff for the final OS analysis after 220 OS events (January 27, 2022), median follow-up duration was 52.4 months. Median OS was 24.6 months (95% confidence interval [CI]: 20.3-31.3) with Isa-Pd and 17.7 months (95% CI: 14.4- 26.2) with Pd (hazard ratio=0.78; 95% CI: 0.59-1.02; 1-sided P=0.0319). Despite subsequent daratumumab use in the Pd group and its potential benefit on PFS in the first subsequent therapy line, median PFS2 was significantly longer with Isa-Pd versus Pd (17.5 vs. 12.9 months; log-rank 1-sided P=0.0091). In this analysis, Isa-Pd continued to be efficacious and well tolerated after follow-up of approximately 52 months, contributing to a clinically meaningful, 6.9-month improvement in median OS in patients with relapsed/refractory multiple myeloma.

Published
2024

7. Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation

Author

Ruggeri, A, de Wreede, L, Muller, C, Crivello, P, Bonneville, E, Petersdorf, E, Socie, G, Dubois, V, Niittyvuopio, R, Perasaari, J, Yakoub-Agha, I, Cornelissen, J, Wieten, L, Gedde-Dahl, T, Forcade, E, Crawley, C, Marsh, S, Gandemer, V, Tholouli, E, Bulabois, C, Huynh, A, Choi, G, Deconinck, E, Itala-Remes, M, Lenhoff, S, Bengtsson, M, Johansson, J, van Gorkom, G, Hoogenboom, J, Vago, L, Rocha, V, Bonini, C, Chabannon, C, Fleischhauer, K, Clausen, J, Holter, W, Kalhs, P, Beguin, Y, Bron, D, Deeren, D, Lung, W, Kerre, T, Poire, X, Selleslag, D, Schroyens, W, Jindra, P, Mayer, J, Vydra, J, Zak, P, Nielsen, B, Sengeloev, H, Kaare, A, Partanen, A, Bay, J, Bertrand, Y, Blaise, D, Bourhis, J, Chevallier, P, Cluzeau, T, Damaj, G, Fegueux, N, Guyotat, D, Hunault-Berger, M, Labussiere-Wallet, H, Leleu, X, Lioure, B, Maury, S, Michel, G, Mohty, M, Rubio, M, Tilly, H, Turlure, P, Bethge, W, Casper, J, Einsele, H, Ganser, A, Kroger, N, Martin, S, Platzbecker, U, Reinhardt, C, Schafer-Eckart, K, Thurner, L, Valerius, T, Wulf, G, Karakasis, D, Spyridonidis, A, Hauser, P, Remenyi, P, Reykdal, S, Mousavi, A, Angelucci, E, Arcese, W, Benedetti, F, Bernasconi, P, Biondi, A, Bonifazi, F, Carella, A, Carluccio, P, Casini, M, Cavanna, L, Ciceri, F, Cimino, G, Corradini, P, Fanin, R, Galieni, P, Grillo, G, Iori, A, La Nasa, G, Locatelli, F, Marotta, G, Martino, M, Mazza, P, Mordini, N, Musso, M, Olivieri, A, Pavone, V, Pane, F, Petrini, M, Pioltelli, P, Rambaldi, A, Ruggeri, M, Saccardi, R, Santarone, S, Scime, R, Sica, S, Tarella, C, Velardi, A, Visani, G, Zecca, M, Tanase, A, Kulagin, A, Savchenko, V, Lopez, C, Amor, A, Lopez, J, Caballero, D, Duarte, R, Cascon, M, Porras, R, Perez-Simon, J, Rovira, M, Sanz, J, Carrete, J, Cammenga, J, Isaksson, C, Mielke, S, Chalandon, Y, Passweg, J, Schanz, U, Meijer, E, Kuball, J, Veelken, J, Apperley, J, Bloor, A, Byrne, J, Carpenter, B, Clark, A, Collin, M, Craddock, C, Gibson, B, Khan, A, Martin, M, Medd, P, Nicholson, E, Orchard, K, Patel, A, Peniket, A, Potter, V, Snowden, J, Wilson, K, Ruggeri A., de Wreede L. C., Muller C. R., Crivello P., Bonneville E. F., Petersdorf E. W., Socie G., Dubois V., Niittyvuopio R., Perasaari J., Yakoub-Agha I., Cornelissen J. J., Wieten L., Gedde-Dahl T., Forcade E., Crawley C. R., Marsh S. G. E., Gandemer V., Tholouli E., Bulabois C. -E., Huynh A., Choi G., Deconinck E., Itala-Remes M., Lenhoff S., Bengtsson M., Johansson J. -E., van Gorkom G., Hoogenboom J. D., Vago L., Rocha V., Bonini C., Chabannon C., Fleischhauer K., Clausen J., Holter W., Kalhs P., Beguin Y., Bron D., Deeren D., Lung W. K., Kerre T., Poire X., Selleslag D., Schroyens W., Jindra P., Mayer J., Vydra J., Zak P., Nielsen B., Sengeloev H., Kaare A., Partanen A., Bay J., Bertrand Y., Blaise D., Bourhis J. H., Chevallier P., Cluzeau T., Damaj G., Fegueux N., Guyotat D., Hunault-Berger M., Labussiere-Wallet H., Leleu X., Lioure B., Maury S., Michel G., Mohty M., Rubio M. T., Tilly H., Turlure P., Bethge W., Casper J., Einsele H., Ganser A., Kroger N., Martin S., Platzbecker U., Reinhardt C., Schafer-Eckart K., Thurner L., Valerius T., Wulf G. G., Karakasis D., Spyridonidis A., Hauser P., Remenyi P., Reykdal S., Mousavi A., Angelucci E., Arcese W., Benedetti F., Bernasconi P., Biondi A., Bonifazi F., Carella A. M., Carluccio P., Casini M., Cavanna L., Ciceri F., Cimino G., Corradini P., Fanin R., Galieni P., Grillo G., Iori A. P., La Nasa G., Locatelli F., Marotta G., Martino M., Mazza P., Mordini N., Musso M., Olivieri A., Pavone V., Pane F., Petrini M., Pioltelli P., Rambaldi A., Ruggeri M., Saccardi R., Santarone S., Scime R., Sica S., Tarella C., Velardi A., Visani G., Zecca M., Tanase A., Kulagin A., Savchenko V., Lopez C. A., Amor A. A., Lopez J. L. B., Caballero D., Duarte R., Cascon M. J. P., Porras R. P., Perez-Simon J. A., Rovira M., Sanz J., Carrete J. P. T., Cammenga J., Isaksson C., Mielke S., Chalandon Y., Passweg J., Schanz U., Meijer E., Kuball J., Veelken J. H., Apperley J., Bloor A., Byrne J., Carpenter B., Clark A., Collin M., Craddock C., Gibson B. E., Khan A., Martin M., Medd P., Nicholson E., Orchard K., Patel A., Peniket A., Potter V., Snowden J., Wilson K. M. O., Ruggeri, A, de Wreede, L, Muller, C, Crivello, P, Bonneville, E, Petersdorf, E, Socie, G, Dubois, V, Niittyvuopio, R, Perasaari, J, Yakoub-Agha, I, Cornelissen, J, Wieten, L, Gedde-Dahl, T, Forcade, E, Crawley, C, Marsh, S, Gandemer, V, Tholouli, E, Bulabois, C, Huynh, A, Choi, G, Deconinck, E, Itala-Remes, M, Lenhoff, S, Bengtsson, M, Johansson, J, van Gorkom, G, Hoogenboom, J, Vago, L, Rocha, V, Bonini, C, Chabannon, C, Fleischhauer, K, Clausen, J, Holter, W, Kalhs, P, Beguin, Y, Bron, D, Deeren, D, Lung, W, Kerre, T, Poire, X, Selleslag, D, Schroyens, W, Jindra, P, Mayer, J, Vydra, J, Zak, P, Nielsen, B, Sengeloev, H, Kaare, A, Partanen, A, Bay, J, Bertrand, Y, Blaise, D, Bourhis, J, Chevallier, P, Cluzeau, T, Damaj, G, Fegueux, N, Guyotat, D, Hunault-Berger, M, Labussiere-Wallet, H, Leleu, X, Lioure, B, Maury, S, Michel, G, Mohty, M, Rubio, M, Tilly, H, Turlure, P, Bethge, W, Casper, J, Einsele, H, Ganser, A, Kroger, N, Martin, S, Platzbecker, U, Reinhardt, C, Schafer-Eckart, K, Thurner, L, Valerius, T, Wulf, G, Karakasis, D, Spyridonidis, A, Hauser, P, Remenyi, P, Reykdal, S, Mousavi, A, Angelucci, E, Arcese, W, Benedetti, F, Bernasconi, P, Biondi, A, Bonifazi, F, Carella, A, Carluccio, P, Casini, M, Cavanna, L, Ciceri, F, Cimino, G, Corradini, P, Fanin, R, Galieni, P, Grillo, G, Iori, A, La Nasa, G, Locatelli, F, Marotta, G, Martino, M, Mazza, P, Mordini, N, Musso, M, Olivieri, A, Pavone, V, Pane, F, Petrini, M, Pioltelli, P, Rambaldi, A, Ruggeri, M, Saccardi, R, Santarone, S, Scime, R, Sica, S, Tarella, C, Velardi, A, Visani, G, Zecca, M, Tanase, A, Kulagin, A, Savchenko, V, Lopez, C, Amor, A, Lopez, J, Caballero, D, Duarte, R, Cascon, M, Porras, R, Perez-Simon, J, Rovira, M, Sanz, J, Carrete, J, Cammenga, J, Isaksson, C, Mielke, S, Chalandon, Y, Passweg, J, Schanz, U, Meijer, E, Kuball, J, Veelken, J, Apperley, J, Bloor, A, Byrne, J, Carpenter, B, Clark, A, Collin, M, Craddock, C, Gibson, B, Khan, A, Martin, M, Medd, P, Nicholson, E, Orchard, K, Patel, A, Peniket, A, Potter, V, Snowden, J, Wilson, K, Ruggeri A., de Wreede L. C., Muller C. R., Crivello P., Bonneville E. F., Petersdorf E. W., Socie G., Dubois V., Niittyvuopio R., Perasaari J., Yakoub-Agha I., Cornelissen J. J., Wieten L., Gedde-Dahl T., Forcade E., Crawley C. R., Marsh S. G. E., Gandemer V., Tholouli E., Bulabois C. -E., Huynh A., Choi G., Deconinck E., Itala-Remes M., Lenhoff S., Bengtsson M., Johansson J. -E., van Gorkom G., Hoogenboom J. D., Vago L., Rocha V., Bonini C., Chabannon C., Fleischhauer K., Clausen J., Holter W., Kalhs P., Beguin Y., Bron D., Deeren D., Lung W. K., Kerre T., Poire X., Selleslag D., Schroyens W., Jindra P., Mayer J., Vydra J., Zak P., Nielsen B., Sengeloev H., Kaare A., Partanen A., Bay J., Bertrand Y., Blaise D., Bourhis J. H., Chevallier P., Cluzeau T., Damaj G., Fegueux N., Guyotat D., Hunault-Berger M., Labussiere-Wallet H., Leleu X., Lioure B., Maury S., Michel G., Mohty M., Rubio M. T., Tilly H., Turlure P., Bethge W., Casper J., Einsele H., Ganser A., Kroger N., Martin S., Platzbecker U., Reinhardt C., Schafer-Eckart K., Thurner L., Valerius T., Wulf G. G., Karakasis D., Spyridonidis A., Hauser P., Remenyi P., Reykdal S., Mousavi A., Angelucci E., Arcese W., Benedetti F., Bernasconi P., Biondi A., Bonifazi F., Carella A. M., Carluccio P., Casini M., Cavanna L., Ciceri F., Cimino G., Corradini P., Fanin R., Galieni P., Grillo G., Iori A. P., La Nasa G., Locatelli F., Marotta G., Martino M., Mazza P., Mordini N., Musso M., Olivieri A., Pavone V., Pane F., Petrini M., Pioltelli P., Rambaldi A., Ruggeri M., Saccardi R., Santarone S., Scime R., Sica S., Tarella C., Velardi A., Visani G., Zecca M., Tanase A., Kulagin A., Savchenko V., Lopez C. A., Amor A. A., Lopez J. L. B., Caballero D., Duarte R., Cascon M. J. P., Porras R. P., Perez-Simon J. A., Rovira M., Sanz J., Carrete J. P. T., Cammenga J., Isaksson C., Mielke S., Chalandon Y., Passweg J., Schanz U., Meijer E., Kuball J., Veelken J. H., Apperley J., Bloor A., Byrne J., Carpenter B., Clark A., Collin M., Craddock C., Gibson B. E., Khan A., Martin M., Medd P., Nicholson E., Orchard K., Patel A., Peniket A., Potter V., Snowden J., and Wilson K. M. O.

Published
2023

8. Outcome in patients with diffuse large B-cell lymphoma who relapse after autologous stem cell transplantation and receive active therapy. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Author

González-Barca, E., Boumendil, A., Blaise, D., Trněný, M., Masszi, T., Finel, H., Michieli, M. G., Bittenbring, J. T., Gritti, G., Snowden, J. A., Bishton, M., Bruno, B., de Villambrosia, S. González, Janikova, A., Leleu, X., Anagnostopoulos, A., Poiré, X., Crysandt, M., Özkurt, Z. N., Vandenberghe, E., Itälä-Remes, M., Cahn, J. Y., Jantunen, E., Schroyens, W., Maertens, J., Esquirol, A., Dreger, P., Montoto, S., and Sureda, A.

Published
2020
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10. EFFICACY AND SAFETY OF ELRANATAMAB IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN–DIRECTED THERAPIES: A POOLED ANALYSIS FROM MAGNETISMM STUDIES

Author

Nooka, A, primary, Lesokhin, A, additional, Mohty, M, additional, Niesvizky, R, additional, Maisel, C, additional, Arnulf, B, additional, Larson, S, additional, Varshavsky-Yanovsky, A, additional, Leleu, X, additional, Karlin, L, additional, Vesole, D, additional, Bahlis, N, additional, Larrea, CF, additional, Raje, N, additional, Leip, E, additional, Conte, U, additional, Elmeliegy, M, additional, Viqueira, A, additional, Blunk, V, additional, and Manier, S, additional

Published
2023
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12. P09 DARATUMUMAB PLUS LENALIDOMIDE AND DEXAMETHASONE (D-RD) VERSUS LENALIDOMIDE AND DEXAMETHASONE (RD) ALONE IN TRANSPLANT-INELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): UPDATED ANALYSIS OF THE PHASE 3 MAIA STUDY

Author

Weisel, K., primary, Kumar, S., additional, Moreau, P., additional, Bahlis, N., additional, Facon, T., additional, Plesner, T., additional, Orlowski, R., additional, Basu, S., additional, Nahi, H., additional, Hulin, C., additional, Quach, H., additional, Goldschmidt, H., additional, O’Dwyer, M., additional, Perrot, A., additional, Venner, C., additional, Raje, N., additional, Tiab1, M., additional, Macro, M., additional, Frenzel, L., additional, Leleu, X., additional, Pei, H., additional, Krevvata, M, additional, Carson, R, additional, Borgsten, F., additional, and Usmani, S., additional

Published
2023
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15. Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma

Author

San-Miguel, J, Dhakal, B, Yong, K, Spencer, A, Anguille, S, Mateos, M-V, Fernandez de Larrea, C, Martinez-Lopez, J, Moreau, P, Touzeau, C, Leleu, X, Avivi, I, Cavo, M, Ishida, T, Kim, SJ, Roeloffzen, W, van de Donk, NWCJ, Dytfeld, D, Sidana, S, Costa, LJ, Oriol, A, Popat, R, Khan, AM, Cohen, YC, Ho, PJ, Griffin, J, Lendvai, N, Lonardi, C, Slaughter, A, Schecter, JM, Jackson, CC, Connors, K, Li, K, Zudaire, E, Chen, D, Gilbert, J, Yeh, T, Nagle, S, Florendo, E, Pacaud, L, Patel, N, Harrison, SJ, Einsele, H, San-Miguel, J, Dhakal, B, Yong, K, Spencer, A, Anguille, S, Mateos, M-V, Fernandez de Larrea, C, Martinez-Lopez, J, Moreau, P, Touzeau, C, Leleu, X, Avivi, I, Cavo, M, Ishida, T, Kim, SJ, Roeloffzen, W, van de Donk, NWCJ, Dytfeld, D, Sidana, S, Costa, LJ, Oriol, A, Popat, R, Khan, AM, Cohen, YC, Ho, PJ, Griffin, J, Lendvai, N, Lonardi, C, Slaughter, A, Schecter, JM, Jackson, CC, Connors, K, Li, K, Zudaire, E, Chen, D, Gilbert, J, Yeh, T, Nagle, S, Florendo, E, Pacaud, L, Patel, N, Harrison, SJ, and Einsele, H

Abstract

BACKGROUND: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease. METHODS: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival. RESULTS: A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2

Published
2023

16. Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation

Author

Ruggeri, A., de Wreede, L. C., Muller, C. R., Crivello, P., Bonneville, E. F., Petersdorf, E. W., Socie, G., Dubois, V., Niittyvuopio, R., Perasaari, J., Yakoub-Agha, I., Cornelissen, J. J., Wieten, L., Gedde-Dahl, T., Forcade, E., Crawley, C. R., Marsh, S. G. E., Gandemer, V., Tholouli, E., Bulabois, C. -E., Huynh, A., Choi, G., Deconinck, E., Itala-Remes, M., Lenhoff, S., Bengtsson, M., Johansson, J. -E., van Gorkom, G., Hoogenboom, J. D., Vago, L., Rocha, V., Bonini, C., Chabannon, C., Fleischhauer, K., Clausen, J., Holter, W., Kalhs, P., Beguin, Y., Bron, D., Deeren, D., Lung, W. K., Kerre, T., Poire, X., Selleslag, D., Schroyens, W., Jindra, P., Mayer, J., Vydra, J., Zak, P., Nielsen, B., Sengeloev, H., Kaare, A., Partanen, A., Bay, J., Bertrand, Y., Blaise, D., Bourhis, J. H., Chevallier, P., Cluzeau, T., Damaj, G., Fegueux, N., Guyotat, D., Hunault-Berger, M., Labussiere-Wallet, H., Leleu, X., Lioure, B., Maury, S., Michel, G., Mohty, M., Rubio, M. T., Tilly, H., Turlure, P., Bethge, W., Casper, J., Einsele, H., Ganser, A., Kroger, N., Martin, S., Platzbecker, U., Reinhardt, C., Schafer-Eckart, K., Thurner, L., Valerius, T., Wulf, G. G., Karakasis, D., Spyridonidis, A., Hauser, P., Remenyi, P., Reykdal, S., Mousavi, A., Angelucci, E., Arcese, W., Benedetti, F., Bernasconi, P., Biondi, A., Bonifazi, F., Carella, A. M., Carluccio, P., Casini, M., Cavanna, L., Ciceri, F., Cimino, G., Corradini, P., Fanin, R., Galieni, P., Grillo, G., Iori, A. P., La Nasa, G., Locatelli, Franco, Marotta, G., Martino, M., Mazza, P., Mordini, N., Musso, M., Olivieri, A., Pavone, V., Pane, F., Petrini, M., Pioltelli, P., Rambaldi, A., Ruggeri, M., Saccardi, R., Santarone, S., Scime, R., Sica, S., Tarella, C., Velardi, A., Visani, G., Zecca, M., Tanase, A., Kulagin, A., Savchenko, V., Lopez, C. A., Amor, A. A., Lopez, J. L. B., Caballero, D., Duarte, R., Cascon, M. J. P., Porras, R. P., Perez-Simon, J. A., Rovira, M., Sanz, J., Carrete, J. P. T., Cammenga, J., Isaksson, C., Mielke, S., Chalandon, Y., Passweg, J., Schanz, U., Meijer, E., Kuball, J., Veelken, J. H., Apperley, J., Bloor, A., Byrne, J., Carpenter, B., Clark, A., Collin, M., Craddock, C., Gibson, B. E., Khan, A., Martin, M., Medd, P., Nicholson, E., Orchard, K., Patel, A., Peniket, A., Potter, V., Snowden, J., Wilson, K. M. O., Locatelli F. (ORCID:0000-0002-7976-3654), Ruggeri, A., de Wreede, L. C., Muller, C. R., Crivello, P., Bonneville, E. F., Petersdorf, E. W., Socie, G., Dubois, V., Niittyvuopio, R., Perasaari, J., Yakoub-Agha, I., Cornelissen, J. J., Wieten, L., Gedde-Dahl, T., Forcade, E., Crawley, C. R., Marsh, S. G. E., Gandemer, V., Tholouli, E., Bulabois, C. -E., Huynh, A., Choi, G., Deconinck, E., Itala-Remes, M., Lenhoff, S., Bengtsson, M., Johansson, J. -E., van Gorkom, G., Hoogenboom, J. D., Vago, L., Rocha, V., Bonini, C., Chabannon, C., Fleischhauer, K., Clausen, J., Holter, W., Kalhs, P., Beguin, Y., Bron, D., Deeren, D., Lung, W. K., Kerre, T., Poire, X., Selleslag, D., Schroyens, W., Jindra, P., Mayer, J., Vydra, J., Zak, P., Nielsen, B., Sengeloev, H., Kaare, A., Partanen, A., Bay, J., Bertrand, Y., Blaise, D., Bourhis, J. H., Chevallier, P., Cluzeau, T., Damaj, G., Fegueux, N., Guyotat, D., Hunault-Berger, M., Labussiere-Wallet, H., Leleu, X., Lioure, B., Maury, S., Michel, G., Mohty, M., Rubio, M. T., Tilly, H., Turlure, P., Bethge, W., Casper, J., Einsele, H., Ganser, A., Kroger, N., Martin, S., Platzbecker, U., Reinhardt, C., Schafer-Eckart, K., Thurner, L., Valerius, T., Wulf, G. G., Karakasis, D., Spyridonidis, A., Hauser, P., Remenyi, P., Reykdal, S., Mousavi, A., Angelucci, E., Arcese, W., Benedetti, F., Bernasconi, P., Biondi, A., Bonifazi, F., Carella, A. M., Carluccio, P., Casini, M., Cavanna, L., Ciceri, F., Cimino, G., Corradini, P., Fanin, R., Galieni, P., Grillo, G., Iori, A. P., La Nasa, G., Locatelli, Franco, Marotta, G., Martino, M., Mazza, P., Mordini, N., Musso, M., Olivieri, A., Pavone, V., Pane, F., Petrini, M., Pioltelli, P., Rambaldi, A., Ruggeri, M., Saccardi, R., Santarone, S., Scime, R., Sica, S., Tarella, C., Velardi, A., Visani, G., Zecca, M., Tanase, A., Kulagin, A., Savchenko, V., Lopez, C. A., Amor, A. A., Lopez, J. L. B., Caballero, D., Duarte, R., Cascon, M. J. P., Porras, R. P., Perez-Simon, J. A., Rovira, M., Sanz, J., Carrete, J. P. T., Cammenga, J., Isaksson, C., Mielke, S., Chalandon, Y., Passweg, J., Schanz, U., Meijer, E., Kuball, J., Veelken, J. H., Apperley, J., Bloor, A., Byrne, J., Carpenter, B., Clark, A., Collin, M., Craddock, C., Gibson, B. E., Khan, A., Martin, M., Medd, P., Nicholson, E., Orchard, K., Patel, A., Peniket, A., Potter, V., Snowden, J., Wilson, K. M. O., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2023

17. Safe and prolonged survival with long-term exposure to pomalidomide in relapsed/refractory myeloma

Author

Fouquet, G., Pegourie, B., Macro, M., Petillon, M.O., Karlin, L., Caillot, D., Roussel, M., Arnulf, B., Mathiot, C., Marit, G., Kolb, B., Stoppa, A.M., Brechiniac, S., Richez, V., Rodon, P., Banos, A., Wetterwald, M., Garderet, L., Royer, B., Hulin, C., Benbouker, L., Decaux, O., Escoffre-Barbe, M., Fermand, J.P., Attal, M., Avet-Loiseau, H., Moreau, P., Facon, T., and Leleu, X.

Published
2016
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18. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study

Author

Kumar, S K, Dimopoulos, M A, Kastritis, E, Terpos, E, Nahi, H, Goldschmidt, H, Hillengass, J, Leleu, X, Beksac, M, Alsina, M, Oriol, A, Cavo, M, Ocio, E M, Mateos, M V, O'Donnell, E K, Vij, R, Lokhorst, H M, van de Donk, N W C J, Min, C, Mark, T, Turesson, I, Hansson, M, Ludwig, H, Jagannath, S, Delforge, M, Kyriakou, C, Hari, P, Mellqvist, U, Usmani, S Z, Dytfeld, D, Badros, A Z, Moreau, P, Kim, K, Otero, P R, Lee, J H, Shustik, C, Waller, D, Chng, W J, Ozaki, S, Lee, J-J, de la Rubia, J, Eom, H S, Rosinol, L, Lahuerta, J J, Sureda, A, Kim, J S, and Durie, B G M

Published
2017
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21. A PHASE 2 TRIAL OF ELRANATAMAB, A B-CELL MATURATION ANTIGEN (BCMA)-CD3 BISPECIFIC ANTIBODY, IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY (R/R) MULTIPLE MYELOMA (MM): INITIAL SAFETY RESULTS FOR MAGNETISMM-3

Author

Lesokhin, AM, primary, Arnulf, B, additional, Niesvizky, R, additional, Mohty, M, additional, Bahlis, NJ, additional, Tomasson, MH, additional, Rodrguez-Otero, P, additional, Quach, H, additional, Raje, NS, additional, Iida, S, additional, Raab, M, additional, Czibere, A, additional, Sullivan, S, additional, Leip, E, additional, Viqueira, A, additional, Blunk, V, additional, and Leleu, X, additional

Published
2022
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23. Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group

Author

Laubach, J, Garderet, L, Mahindra, A, Gahrton, G, Caers, J, Sezer, O, Voorhees, P, Leleu, X, Johnsen, H E, Streetly, M, Jurczyszyn, A, Ludwig, H, Mellqvist, U-H, Chng, W-J, Pilarski, L, Einsele, H, Hou, J, Turesson, I, Zamagni, E, Chim, C S, Mazumder, A, Westin, J, Lu, J, Reiman, T, Kristinsson, S, Joshua, D, Roussel, M, O'Gorman, P, Terpos, E, McCarthy, P, Dimopoulos, M, Moreau, P, Orlowski, R Z, Miguel, J S, Anderson, K C, Palumbo, A, Kumar, S, Rajkumar, V, Durie, B, and Richardson, P G

Published
2016
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25. B-cell malignancies: capture-sequencing strategies for identification of gene rearrangements and translocations into immunoglobulin gene loci

Author

Boyle EM, Walker BA, Wardell CP, Leleu X, Davies FE, and Morgan GJ

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Eileen M Boyle,1,2 Brian A Walker,1 Christopher P Wardell,1 Xavier Leleu,2 Faith E Davies,1 Gareth J Morgan1 1Centre for Myeloma Research, Institute of Cancer Research, Sutton, Surrey, UK; 2Service des Maladies du Sang, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France Abstract: Aberrant chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus and clonal rearrangements of the variable (V), diversity (D), joining (J) segments (V[D]J) of the immunoglobulin gene are implicated in the initiation of mature B-cell malignancies, including myeloma. Analysis of these events provides information useful for diagnosis and prediction of prognosis, and also provides a useful monitoring strategy for response to treatment in patients with these diseases. Current methods for identification of these events are not generally applicable and give a biased picture of the prognostic significance and clinical relevance of these events. Novel methodologies based on next-generation sequencing are a new and more efficient genetic tool that can be used to screen and characterize these changes at the nucleotide level, offering a deeper and better understanding of the genetic basis of these complex diseases. In this work, we provide a review of the molecular basis of B-cell neoplasms, the methods used to detect them, and how they translate into the clinic. Keywords: B-cell malignancies, minimal residual disease, molecular, IGH locus, next-generation sequencing

Published
2014

26. S184: EVALUATING TECLISTAMAB IN PATIENTS WITH RELAPSED/ REFRACTORY MULTIPLE MYELOMA FOLLOWING EXPOSURE TO OTHER B-CELL MATURATION ANTIGEN (BCMA)-TARGETED AGENTS

Author

Touzeau, C., primary, Krishnan, A., additional, Moreau, P., additional, Perrot, A., additional, Usmani, S. Z., additional, Manier, S., additional, Cavo, M., additional, Martinez-Chamorro, C., additional, Nooka, A., additional, Martin, T., additional, Karlin, L., additional, Leleu, X., additional, Bahlis, N., additional, Besemer, B., additional, Pei, L., additional, Verona, R., additional, Girgis, S., additional, Uhlar, C., additional, Kobos, R., additional, and Garfall, A., additional

Published
2022
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27. P872: DEL(1P32) REMAINS A POWERFUL PROGNOSTIC FACTOR IN A LARGE COHORT OF NDMM PATIENTS: AN UPDATE

Author

Schavgoulidze, A., primary, Perrot, A., additional, Cazaubiel, T., additional, Leleu, X., additional, Manier, S., additional, Buisson, L., additional, Maheo, S., additional, Do Souto Ferreira, L., additional, Lannes, R., additional, Pavageau, L., additional, Hulin, C., additional, Marolleau, J.-P., additional, Voillat, L., additional, Belhadj, K., additional, Divoux, M., additional, Slama, B., additional, Brechignac, S., additional, Macro, M., additional, Stoppa, A.-M., additional, Sanhes, L., additional, Orsini-Piocelle, F., additional, Fontan, J., additional, Chretien, M.-L., additional, Demarquette, H., additional, Mohty, M., additional, Avet-Loiseau, H., additional, and Corre, J., additional

Published
2022
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28. P925: IMPACT OF PRIOR TREATMENT EXPOSURE ON THE EFFECTIVENESS OF IXAZOMIB-LENALIDOMIDE-DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS TREATED IN ROUTINE CLINICAL PRACTICE (THE INSURE STUDY)

Author

Lee, H. C., primary, Ramasamy, K., additional, Macro, M., additional, Davies, F. E., additional, Abonour, R., additional, van Rhee, F., additional, Hungria, V. T., additional, Puig, N., additional, Ren, K., additional, Silar, J., additional, Enwemadu, V., additional, Cherepanov, D., additional, Stull, D. M., additional, and Leleu, X., additional

Published
2022
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30. P956: EMMY COHORT: MANAGEMENT OF NEWLY DIAGNOSED OR RELAPSED/ REFRACTORY MULTIPLE MYELOMA IN PATIENTS AGED OF 80 YEARS AND OVER

Author

Macro, M., primary, Decaux, O., additional, Perrot, A., additional, Royer, B., additional, Chretien, M., additional, Belhadj, K., additional, Mohty, M., additional, Frenzel, L., additional, Leleu, X., additional, Dib, M., additional, Allangba, O., additional, Zunic, P., additional, Botoc, I., additional, Malfuson, J., additional, Moreau, P., additional, Garlantazec, R., additional, Texier, N., additional, Germain, R., additional, Deal, C., additional, and Hulin, C., additional

Published
2022
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31. P929: IXAZOMIB AND DARATUMUMAB WITHOUT DEXAMETHASONE (I-DARA) IN ELDERLY FRAIL RELAPSING MYELOMA (RRMM) PATIENTS: RESULTS OF THE PHASE 2 STUDY IFM 2018-02 OF THE INTERGROUPE FRANCOPHONE DU MYELOME (IFM).

Author

Macro, M., primary, Touzeau, C., additional, Mariette, C., additional, Manier, S., additional, Brechignac, S., additional, Vincent, L., additional, Hebraud, B., additional, Decaux, O., additional, Schulmann, S., additional, Lenoir, C., additional, Godmer, P., additional, Farge, A., additional, Peyro Saint Paul, L., additional, Parienti, J.-J., additional, and Leleu, X., additional

Published
2022
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33. P891: IXAZOMIB, POMALIDOMIDE AND DEXAMETHASONE (IXPD) IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM) CHARACTERIZED WITH HIGH-RISK CYTOGENETICS. IFM 2014-01

Author

Bobin, A., primary, Manier, S., additional, De Keizer, J., additional, Karlin, L., additional, Perrot, A., additional, Hulin, C., additional, Caillot, D., additional, Mariette, C., additional, Lenain, P., additional, Richez, V., additional, Tiab, M., additional, Touzeau, C., additional, Jaccard, A., additional, Decaux, O., additional, Araujo, C., additional, Belhadj, K., additional, Benboubker, L., additional, Déal, C., additional, Macro, M., additional, Vincent, L., additional, Arnulf, B., additional, Bareau, B., additional, Braun, T., additional, Calmettes, C., additional, mamoun, D., additional, Zerazhi, H., additional, Demarquette, H., additional, Feugier, P., additional, Fohrer-sonntag, C., additional, Godet, S., additional, Petillon, M.-O., additional, Avet-Loiseau, H., additional, and Leleu, X., additional

Published
2022
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34. P942: DREAMM-9: PHASE I STUDY OF BELANTAMAB MAFODOTIN PLUS STANDARD OF CARE IN PATIENTS WITH TRANSPLANT-INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA

Author

Usmani, S. Z., primary, Mielnik, M., additional, Koh, Y., additional, Alonso Alonso, A., additional, Leleu, X., additional, Quach, H., additional, Min, C.-K., additional, Janowski, W., additional, Abdallah, A.-O., additional, Garg, M., additional, Sandhu, I., additional, Ocio San Miguel, E. M., additional, Oriol, A., additional, Rodriquez-Otero, P., additional, Ramasamy, K., additional, Weisel, K., additional, Besemer, B., additional, Cavo, M., additional, Zhou, X. L., additional, Kaisermann, M. C., additional, Bego Marques, C. M., additional, Williams, D., additional, Carreno, F., additional, Kremer, B. E., additional, Gupta, I. V., additional, and Hus, M., additional

Published
2022
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35. S176: DARATUMUMAB CARFILZOMIB LENALIDOMIDE AND DEXAMETHASONE AS INDUCTION THERAPY IN HIGH-RISK TRANSPLANT ELIGIBLE NEWLY DIAGNOSED MYELOMA PATIENTS: RESULTS OF THE PHASE 2 STUDY IFM 2018-04

Author

Touzeau, C., primary, Perrrot, A., additional, Hulin, C., additional, Manier, S., additional, Macro, M., additional, Chretien, M.-L., additional, Karlin, L., additional, Decaux, O., additional, Jacquet, C., additional, Tiab, M., additional, Leleu, X., additional, Planchce, L., additional, Avet-Loiseau, H., additional, and Moreau, P., additional

Published
2022
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36. P936: TIME TO RESPONSE, DURATION OF RESPONSE, AND PATIENT-REPORTED OUTCOMES WITH DARATUMUMAB PLUS RD VS RD ALONE IN TRANSPLANT-INELIGIBLE PATIENTS WITH NDMM: SUBGROUP ANALYSIS OF THE PHASE 3 MAIA STUDY

Author

Facon, T., primary, Kumar, S. K., additional, Plesner, T., additional, Moreau, P., additional, Bahlis, N., additional, Goldschmidt, H., additional, O’Dwyer, M., additional, Perrot, A., additional, Venner, C. P., additional, Weisel, K., additional, Mace, J. R., additional, Raje, N., additional, Tiab, M., additional, Macro, M., additional, Frenzel, L., additional, Leleu, X., additional, Pei, H., additional, Borgsten, F., additional, and Usmani, S. Z., additional

Published
2022
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37. P949: A PHASE 2 TRIAL OF ELRANATAMAB, A B-CELL MATURATION ANTIGEN (BCMA)-CD3 BISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL SAFETY RESULTS FOR MAGNETISMM-3

Author

Lesokhin, A. M., primary, Arnulf, B., additional, Niesvizky, R., additional, Mohty, M., additional, Bahlis, N. J., additional, Tomasson, M. H., additional, Rodrίguez-Otero, P., additional, Quach, H., additional, Raje, N. S., additional, Iida, S., additional, Raab, M.-S., additional, Czibere, A., additional, Sullivan, S., additional, Leip, E., additional, Viqueira, A., additional, and Leleu, X., additional

Published
2022
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38. Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial

Author

Dimopoulos, M. A., Špička, I., Quach, H., Oriol, Albert, Hájek, R., Garg, M., Beksac, M., Bringhen, S., Katodritou, E., Chng, W. J., Leleu, X., Iida, S., Mateos, M. V., Morgan, G., Vorog, A., Labotka, R., Wang, B., Palumbo, A., Lonial, S., Universitat Autònoma de Barcelona, and Millennium Pharmaceuticals

Subjects
Boron Compounds, Male, Oncology, Cancer Research, medicine.medical_specialty, Glycine, Antineoplastic Agents, Newly diagnosed, Maintenance Chemotherapy, Ixazomib, law.invention, Placebos, chemistry.chemical_compound, Autologous stem-cell transplantation, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Hematologic Malignancy, medicine, Humans, In patient, Progression-free survival, Multiple myeloma, Aged, business.industry, ORIGINAL REPORTS, Middle Aged, medicine.disease, Progression-Free Survival, Clinical trial, Treatment Outcome, chemistry, Female, Multiple Myeloma, business, Proteasome Inhibitors, Stem Cell Transplantation
Abstract

© 2020 by American Society of Clinical Oncology., [Purpose]: Maintenance therapy prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing autologous stem cell transplantation (ASCT) but has generally been limited to immunomodulatory agents. Other options that complement the induction regimen with favorable toxicity are needed., [Patients and Methods]: The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study randomly assigned (3:2) patients with NDMM not undergoing ASCT who achieved better than or equal to partial response after 6-12 months of standard induction therapy to receive the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months. The primary endpoint was PFS since time of randomization., [Results]: Patients were randomly assigned to receive ixazomib (n = 425) or placebo (n = 281). TOURMALINE-MM4 met its primary endpoint with a 34.1% reduction in risk of progression or death with ixazomib versus placebo (median PFS since randomization, 17.4 v 9.4 months; hazard ratio [HR], 0.659; 95% CI, 0.542 to 0.801; P < .001; median follow-up, 21.1 months). Ixazomib significantly benefitted patients who achieved complete or very good partial response postinduction (median PFS, 25.6 v 12.9 months; HR, 0.586; P < .001). With ixazomib versus placebo, 36.6% versus 23.2% of patients had grade ≥ 3 treatment-emergent adverse events (TEAEs); 12.9% versus 8.0% discontinued treatment because of TEAEs. Common any-grade TEAEs included nausea (26.8% v 8.0%), vomiting (24.2% v 4.3%), and diarrhea (23.2% v 12.3%). There was no increase in new primary malignancies (5.2% v 6.2%); rates of on-study deaths were 2.6% versus 2.2%., [Conclusio]:Ixazomib maintenance prolongs PFS with no unexpected toxicity in patients with NDMM not undergoing ASCT. To our knowledge, this is the first PI demonstrated in a randomized clinical trial to have single-agent efficacy for maintenance and is the first oral PI option in this patient population., This study was sponsored by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. T

Published
2020
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39. P14: DREAMM-9: PHASE I STUDY OF BELANTAMAB MAFODOTIN PLUS STANDARD OF CARE IN PATIENTS WITH TRANSPLANT-INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA

Author

Usmani, S, Alonso, A, Quach, H, Koh, Y, Guenther, A, Min, CK, Leleu, X, Abdallah, AO, Oriol, A, Bessemer, B, Garg, M, Sandhu, I, Weisel, K, Ocio San Miguel, E, Cavo, M, Zhou, X, Kaisermann, M, Mis, L, Williams, D, Yeakey, A, Ferron-Brady, G, Figueroa, D, Kremer, B, Gupta, I, Janowski, W, Usmani, S, Alonso, A, Quach, H, Koh, Y, Guenther, A, Min, CK, Leleu, X, Abdallah, AO, Oriol, A, Bessemer, B, Garg, M, Sandhu, I, Weisel, K, Ocio San Miguel, E, Cavo, M, Zhou, X, Kaisermann, M, Mis, L, Williams, D, Yeakey, A, Ferron-Brady, G, Figueroa, D, Kremer, B, Gupta, I, and Janowski, W

Published
2022

40. Efficacy and tolerability of once-weekly selinexor, bortezomib, and dexamethasone in comparison with standard twice-weekly bortezomib and dexamethasone in previously treated multiple myeloma with renal impairment: Subgroup analysis from the BOSTON study

Author

Delimpasi, S, Mateos, MV, Auner, HW, Gavriatopoulou, M, Dimopoulos, MA, Quach, H, Pylypenko, H, Hajek, R, Leleu, X, Dolai, TK, Sinha, DK, Venner, CP, Benjamin, R, Garg, MK, Doronin, V, Levy, Y, Moreau, P, Chai, Y, Arazy, M, Shah, J, Shacham, S, Kauffman, MG, Richardson, PG, Grosicki, S, Delimpasi, S, Mateos, MV, Auner, HW, Gavriatopoulou, M, Dimopoulos, MA, Quach, H, Pylypenko, H, Hajek, R, Leleu, X, Dolai, TK, Sinha, DK, Venner, CP, Benjamin, R, Garg, MK, Doronin, V, Levy, Y, Moreau, P, Chai, Y, Arazy, M, Shah, J, Shacham, S, Kauffman, MG, Richardson, PG, and Grosicki, S

Published
2022

41. Oral ixazomib-dexamethasone vs oral pomalidomide-dexamethasone for lenalidomide-refractory, proteasome inhibitor-exposed multiple myeloma: a randomized Phase 2 trial

Author

Dimopoulos, MA, Schjesvold, F, Doronin, V, Vinogradova, O, Quach, H, Leleu, X, Montes, YG, Ramasamy, K, Pompa, A, Levin, M-D, Lee, C, Mellqvist, UH, Fenk, R, Demarquette, H, Sati, H, Vorog, A, Labotka, R, Du, J, Darif, M, Kumar, S, Dimopoulos, MA, Schjesvold, F, Doronin, V, Vinogradova, O, Quach, H, Leleu, X, Montes, YG, Ramasamy, K, Pompa, A, Levin, M-D, Lee, C, Mellqvist, UH, Fenk, R, Demarquette, H, Sati, H, Vorog, A, Labotka, R, Du, J, Darif, M, and Kumar, S

Abstract

Multiple myeloma (MM) patients typically receive several lines of combination therapy and first-line treatment commonly includes lenalidomide. As patients age, they become less tolerant to treatment, requiring convenient/tolerable/lenalidomide-free options. Carfilzomib and/or bortezomib-exposed/intolerant, lenalidomide-refractory MM patients with ≥2 prior lines of therapy were randomized 3:2 to ixazomib-dexamethasone (ixa-dex) (n = 73) or pomalidomide-dexamethasone (pom-dex) (n = 49) until progression/toxicity. Median progression-free survival (mPFS) was 7.1 vs 4.8 months with ixa-dex vs pom-dex (HR 0.847, 95% CI 0.535-1.341, P = 0.477; median follow-up: 15.3 vs 17.3 months); there was no statistically significant difference between arms. In patients with 2 and ≥3 prior lines of therapy, respectively, mPFS was 11.0 vs 5.7 months (HR 1.083, 95% CI 0.547-2.144) and 5.7 vs 3.7 months (HR 0.686, 95% CI 0.368-1.279). Among ixa-dex vs pom-dex patients, 69% vs 81% had Grade ≥3 treatment-emergent adverse events (TEAEs), 51% vs 53% had serious TEAEs, 39% vs 36% had TEAEs leading to drug discontinuation, 44% vs 32% had TEAEs leading to dose reduction, and 13% vs 13% died on study. Quality of life was similar between arms and maintained during treatment. Ixa-dex represents an important lenalidomide-free, oral option for this heavily pretreated, lenalidomide-refractory, proteasome inhibitor-exposed population.Trial registration: ClinicalTrials.gov number, NCT03170882.

Published
2022

42. Anti-CD38 antibody therapy for patients with relapsed/refractory multiple myeloma: differential mechanisms of action and recent clinical trial outcomes

Author

Leleu, X, Martin, T, Weisel, K, Schjesvold, F, Iida, S, Malavasi, F, Manier, S, Min, C-K, Ocio, EM, Pawlyn, C, Perrot, A, Quach, H, Richter, J, Spicka, I, Yong, K, Richardson, PG, Leleu, X, Martin, T, Weisel, K, Schjesvold, F, Iida, S, Malavasi, F, Manier, S, Min, C-K, Ocio, EM, Pawlyn, C, Perrot, A, Quach, H, Richter, J, Spicka, I, Yong, K, and Richardson, PG

Abstract

CD38 is a transmembrane glycoprotein that functions both as a receptor and an ectoenzyme, playing key roles in the regulation of calcium signaling and migration of immune cells to tumor microenvironments. High expression on multiple myeloma (MM) cells and limited expression on normal cells makes CD38 an ideal target for the treatment of MM patients. Two monoclonal antibodies directed at CD38, isatuximab and daratumumab, are available for use in patients with relapsed and/or refractory MM (RRMM); daratumumab is also approved in newly diagnosed MM and light-chain amyloidosis. Clinical experience has shown that anti-CD38 antibody therapy is transforming treatment of MM owing to its anti-myeloma efficacy and manageable safety profile. Isatuximab and daratumumab possess similarities and differences in their mechanisms of action, likely imparted by their binding to distinct, non-overlapping epitopes on the CD38 molecule. In this review, we present the mechanistic properties of these two antibodies and outline available evidence on their abilities to induce adaptive immune responses and modulate the bone marrow niche in MM. Further, we discuss differences in regulatory labeling between these two agents and analyze recent key clinical trial results, including evidence in patients with underlying renal impairment and other poor prognostic factors. Finally, we describe the limited existing evidence for the use of isatuximab or daratumumab after disease progression on prior anti-CD38 mono- or combination therapy, highlighting the need for additional clinical evaluations to define optimal anti-CD38 antibody therapy selection and sequencing in RRMM.

Published
2022

43. Isatuximab Plus Pomalidomide/Low-Dose Dexamethasone Versus Pomalidomide/Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (ICARIA-MM): Characterization of Subsequent Antimyeloma Therapies

Author

Richardson, PG, Perrot, A, San-Miguel, J, Beksac, M, Spicka, I, Leleu, X, Schjesvold, F, Moreau, P, Dimopoulos, MA, Huang, JSY, Minarik, J, Cavo, M, Prince, HM, Macé, S, Malinge, L, Dubin, F, Morisse, M, Anderson, KC, Richardson, PG, Perrot, A, San-Miguel, J, Beksac, M, Spicka, I, Leleu, X, Schjesvold, F, Moreau, P, Dimopoulos, MA, Huang, JSY, Minarik, J, Cavo, M, Prince, HM, Macé, S, Malinge, L, Dubin, F, Morisse, M, and Anderson, KC

Abstract

Introduction: Based on the primary analysis of the Phase 3 ICARIA-MM study (NCT02990338), isatuximab (Isa), an anti-CD38 monoclonal antibody, is approved in combination with pomalidomide and dexamethasone (Pd) in several countries for patients with relapsed and refractory multiple myeloma (RRMM) who have received at least 2 prior treatments, including lenalidomide and a proteasome inhibitor. Here, we describe updated, longer-term efficacy data following subsequent therapy. Methods: Patients were randomized 1:1 to Isa-Pd (n=154) or Pd (n=153), with stratification by age (<75 vs ≥75) and number of prior lines (2-3 versus more than >3). Isa 10 mg/kg was administered weekly for the first 4-week cycle and every 2 weeks thereafter. In each cycle, both treatment arms received pomalidomide 4 mg (days 1-21) and weekly dexamethasone 40 mg (days 1, 8, 15, and 22). Treatment was given until progressive disease, unacceptable adverse events, or patient choice. The final overall survival analysis was planned when 220 death events occurred. Results: As of March 14, 2022, 16 (10.4%) patients receiving Isa-Pd and 3 (2.0%) patients receiving Pd were still on treatment; 101 (65.6%) and 117 (76.5%) patients, respectively, discontinued treatment due to progressive disease. Median treatment duration was longer with Isa-Pd vs Pd (47.6 vs 24.0 weeks). After a median 52.4 months of follow-up, a clinically meaningful overall survival (OS) benefit was observed in favor of Isa-Pd vs Pd after 220 events (Jan 27, 2022; median: 24.6 vs 17.7 months; hazard ratio 0.776 [95% CI: 0.594-1.1015]; one-sided P=0.0319; significance level: P=0.02). Further antimyeloma treatment was given to 102 (66.2%) patients receiving Isa-Pd and 119 (77.8%) patients receiving Pd (regardless of the reason for treatment discontinuation in both arms), with a median of 2 and 1 further regimens, respectively. Of the patients receiving subsequent therapy, 22.5% (23/102) in the Isa-Pd arm and 59.7% (71/119) in the Pd arm receiv

Published
2022

44. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)

Author

Hájek, R, Masszi, T, Petrucci, M T, Palumbo, A, Rosiñol, L, Nagler, A, Yong, K L, Oriol, A, Minarik, J, Pour, L, Dimopoulos, M A, Maisnar, V, Rossi, D, Kasparu, H, Van Droogenbroeck, J, Yehuda, D B, Hardan, I, Jenner, M, Calbecka, M, Dávid, M, de la Rubia, J, Drach, J, Gasztonyi, Z, Górnik, S, Leleu, X, Munder, M, Offidani, M, Zojer, N, Rajangam, K, Chang, Y-L, San-Miguel, J F, and Ludwig, H

Published
2017
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46. P24: EXPERT PERSPECTIVES OF UNMET NEED IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM) WHO RECEIVE LENALIDOMIDE-SPARING REGIMENS IN EUROPE

Author

Mateos, M, primary, Leleu, X, additional, Zamagni, E, additional, Delforge, M, additional, Bringhen, S, additional, Broijl, A, additional, de la Rubia, J, additional, Shaw, A, additional, Brescianini, A, additional, Gonzalez-McQuire, S, additional, Patel, S, additional, and Moreau, P, additional

Published
2022
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47. An overview of treatment options for patients with relapsed/refractory multiple myeloma and renal impairment

Author

Dimopoulos, M.A. Mikhael, J. Terpos, E. Leleu, X. Moreau, P. Bladé, J. Kim, J.S. Stockerl-Goldstein, K. Richardson, P.G.

Abstract

Renal impairment (RI) is a relatively common complication of multiple myeloma, which increases in frequency as disease becomes more advanced and recovery of renal function becomes less likely as patients progress through lines of therapy. Clinical trials in the relapsed/refractory multiple myeloma (RRMM) setting have not uniformly included patients with RI or robustly reported their outcomes. Here, we review existing data among patients with RI and RRMM across drug classes (including immunomodulatory agents, proteasome inhibitors, monoclonal antibodies, antibody-drug conjugates, chimeric antigen receptor T-cell therapies, and exportin-1 inhibitor) to provide an improved understanding of available treatment options for this important population. We highlight data from pivotal clinical trials, including data relating to renal response (as defined by the International Myeloma Working Group) and discuss real-world experiences in patients with RI, where applicable. Despite substantial advances in RRMM treatment, the presence of RI remains associated with reduced overall survival. Consistent inclusion of patients with RI, and uniform reporting of their outcomes, should be encouraged in future prospective trials of treatments for RRMM. © The Author(s), 2022.

Published
2022

48. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study

Author

Usmani, S.Z. Quach, H. Mateos, M.-V. Landgren, O. Leleu, X. Siegel, D. Weisel, K. Gavriatopoulou, M. Oriol, A. Rabin, N. Nooka, A. Qi, M. Beksac, M. Jakubowiak, A. Ding, B. Zahlten-Kumeli, A. Yusuf, A. Dimopoulos, M.

Abstract

Background: Despite recent advances in therapeutic options, there remains an unmet need for treating patients with relapsed or refractory multiple myeloma, especially in those previously exposed or refractory to lenalidomide. This updated efficacy and safety analysis from the phase 3 CANDOR study compared carfilzomib, daratumumab, and dexamethasone (KdD) with carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma. Methods: In this updated analysis of the randomised, multicentre, open-label, phase 3 CANDOR study, patients (aged ≥18 years) with relapsed or refractory multiple myeloma, at least a partial response to between one and three previous therapies, and Eastern Cooperative Oncology Group performance status of 0–2, were recruited from 102 medical centres globally and randomly assigned (2:1) by interactive voice or web response software to receive KdD or Kd. Participants were stratified by disease stage, previous proteasome inhibitor or anti-CD38 antibody exposure, and number of previous therapies. All patients received intravenous infusions of carfilzomib twice per week at 56 mg/m2 (20 mg/m2 on days 1 and 2 during cycle 1) on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Daratumumab (8 mg/kg) was administered intravenously on days 1 and 2 of cycle 1 and at 16 mg/kg weekly for the remaining doses of the first two cycles, then every 2 weeks for four cycles (cycles 3–6), and every 4 weeks thereafter. Patients received 40 mg dexamethasone weekly (20 mg for patients >75 years old). This analysis was a preplanned interim analysis for overall survival; however, at the time of data cutoff, overall survival data were not mature. The primary endpoint was progression-free survival. Here, we provide updated progression-free survival data, assessed centrally by Onyx Response Computer Algorithm in the intention-to-treat population, with 11 months additional follow-up. Adverse events were assessed in the safety population, which included all participants who received at least one dose of trial treatment. CANDOR is registered with ClinicalTrials.gov, NCT03158688, and is active but not recruiting. Findings: Between June 13, 2017, and June 25, 2018, 466 patients were enrolled, of whom 312 received KdD and 154 received Kd. At data cutoff (June 15, 2020), median follow-up was 27·8 months (IQR 25·6–29·5) for KdD and 27·0 months (13·2–28·6) for Kd. Median progression-free survival was 28·6 months (95% CI 22·7–not estimable [NE]) in the KdD group and 15·2 months (11·1–19·9) in the Kd group (hazard ratio 0·59 [95% CI 0·45–0·78], log-rank p

Published
2022

49. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study

Author

Usmani SZ, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Gavriatopoulou M, Oriol A, Rabin N, Nooka A, Qi M, Beksac M, Jakubowiak A, Ding B, Zahlten-Kumeli A, Yusuf A, and Dimopoulos M

Abstract

BACKGROUND: Despite recent advances in therapeutic options, there remains an unmet need for treating patients with relapsed or refractory multiple myeloma, especially in those previously exposed or refractory to lenalidomide. This updated efficacy and safety analysis from the phase 3 CANDOR study compared carfilzomib, daratumumab, and dexamethasone (KdD) with carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma. METHODS: In this updated analysis of the randomised, multicentre, open-label, phase 3 CANDOR study, patients (aged =18 years) with relapsed or refractory multiple myeloma, at least a partial response to between one and three previous therapies, and Eastern Cooperative Oncology Group performance status of 0-2, were recruited from 102 medical centres globally and randomly assigned (2:1) by interactive voice or web response software to receive KdD or Kd. Participants were stratified by disease stage, previous proteasome inhibitor or anti-CD38 antibody exposure, and number of previous therapies. All patients received intravenous infusions of carfilzomib twice per week at 56 mg/m(2) (20 mg/m(2) on days 1 and 2 during cycle 1) on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Daratumumab (8 mg/kg) was administered intravenously on days 1 and 2 of cycle 1 and at 16 mg/kg weekly for the remaining doses of the first two cycles, then every 2 weeks for four cycles (cycles 3-6), and every 4 weeks thereafter. Patients received 40 mg dexamethasone weekly (20 mg for patients >75 years old). This analysis was a preplanned interim analysis for overall survival; however, at the time of data cutoff, overall survival data were not mature. The primary endpoint was progression-free survival. Here, we provide updated progression-free survival data, assessed centrally by Onyx Response Computer Algorithm in the intention-to-treat population, with 11 months additional follow-up. Adverse events were assessed in the safety population, which included all participants who received at least one dose of trial treatment. CANDOR is registered with ClinicalTrials.gov, NCT03158688, and is active but not recruiting. FINDINGS: Between June 13, 2017, and June 25, 2018, 466 patients were enrolled, of whom 312 received KdD and 154 received Kd. At data cutoff (June 15, 2020), median follow-up was 27·8 months (IQR 25·6-29·5) for KdD and 27·0 months (13·2-28·6) for Kd. Median progression-free survival was 28·6 months (95% CI 22·7-not estimable [NE]) in the KdD group and 15·2 months (11·1-19·9) in the Kd group (hazard ratio 0·59 [95% CI 0·45-0·78], log-rank p

Published
2022

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